1. Field of the Invention
The present invention relates to novel compounds having corticotropin-releasing factor (hereinafter, referred to as “CRF”) receptor antagonistic activity, and pharmacologically acceptable salts thereof and to medical use of the same.
2. Related Background Art
CRF is a neuropeptide that consists of 41 amino acids and is produced and secreted in the hypothalamus and promotes release of adrenocorticotropic hormone (ACTH) under stress, and it also functions in the brain as a neurotransmitter or a neuromodulator, integrating electrophysiology, autonomic nerves, behavior, and the like, in response to stress.
There are two subtypes in CRF receptors, CRF1 receptor and CRF2 receptor, and CRF1 receptor has been reported to be widely distributed in the cerebral cortex, cerebellum, olfactory bulb, pituitary gland, amygdaloid nucleus, and the like.
Furthermore, many low molecular compounds having CRF receptor antagonism have been noted as potential therapeutic agents for a variety of diseases including depression, anxiety, stress-related disorders, and the like (see Non-patent Document 1).
Disclosed compounds having CRF receptor antagonism include compounds having a 2,6-dimethoxy-4-methoxymethylphenyl group (see Patent Document 1), but compounds having a pyrazolo[5,1-b]thiazole skeleton according to the invention of the present application have been neither disclosed nor suggested.
As a compound having a pyrazolo[5,1-b]thiazole skeleton, the compound shown below has been disclosed but its use is for colorimetry (see Example 16 of Patent Document 2).

Patent Document 3 (international filing date: Oct. 22, 2009) discloses the following compounds which have a pyrazolo[5,1-b]thiazole skeleton and have CRF receptor antagonism

wherein R1 is the formula -A11-A12, R2 is tetrahydrofurylmethyl, tetrahydropyranylmethyl or tetrahydropyranyl, A11 is a single bond, methylene or 1,2-ethylene, A12 is C1-6 alkyl, C3-6 cycloalkyl or C3-6 cycloalkyl having methyl, R3 is methoxy, cyano, cyclobutyloxymethyl, methoxymethyl or ethoxymethyl, and R4 is methoxy or chlorine.
Patent Document 3 was published after the filing date of the earliest priority applications (Japanese patent application No. 2009-233989 and U.S. provisional application No. 61/249,817; both were filed on Oct. 8, 2009) of the present application.